The Effect of a Maternal Mediterranean Diet in Pregnancy on Insulin Resistance is Moderated by Maternal Negative Affect.

There is inconsistent evidence that healthy dietary interventions can effectively mitigate the risk of adverse outcomes associated with elevated insulin resistance in pregnancy, suggesting that other moderating factors may be at play. Maternal psychological state is an important factor to consider in this regard, because stress/mood state can directly influence glycemia and a bidirectional relationship may exist between nutrition and psychological state. The objective of this study was to examine the interaction between maternal negative affect and diet quality on third trimester insulin resistance. We conducted a prospective longitudinal study of N = 203 women with assessments in early and mid-pregnancy, which included an ecological momentary assessment of maternal psychological state, from which a negative affect score (NAS) was derived, and 24-h dietary recalls, from which the Mediterranean Diet Score (MDS) was computed. The homeostasis model assessment of insulin resistance (HOMA-IR) was computed from third trimester fasting plasma glucose and insulin values. Early pregnancy MDS was inversely associated with the HOMA-IR, but this did not maintain significance after adjusting for covariates. There was a significant effect of the mid-pregnancy MDS*NAS interaction term with the HOMA-IR in the adjusted model, such that a higher negative affect was found to override the beneficial effects of a Mediterranean diet on insulin resistance. These results highlight the need to consider nutrition and affective state concurrently in the context of gestational insulin resistance

Neonatal White Matter Maturation Is Associated With Infant Language Development

Background: While neonates have no sophisticated language skills, the neural basis for acquiring this function is assumed to already be present at birth. Receptive language is measurable by 6 months of age and meaningful speech production by 10-18 months of age. Fiber tracts supporting language processing include the corpus callosum (CC), which plays a key role in the hemispheric lateralization of language; the left arcuate fasciculus (AF), which is associated with syntactic processing; and the right AF, which plays a role in prosody and semantics. We examined if neonatal maturation of these fiber tracts is associated with receptive language development at 12 months of age. Methods: Diffusion-weighted imaging (DWI) was performed in 86 infants at 26.6 ± 12.2 days post-birth. Receptive language was assessed via the MacArthur-Bates Communicative Development Inventory at 12 months of age. Tract-based fractional anisotropy (FA) was determined using the NA-MIC atlas-based fiber analysis toolkit. Associations between neonatal regional FA, adjusted for gestational age at birth and age at scan, and language development at 12 months of age were tested using ANOVA models. Results: After multiple comparisons correction, higher neonatal FA was positively associated with receptive language at 12 months of age within the genu (p < 0.001), rostrum (p < 0.001), and tapetum (p < 0.001) of the CC and the left fronto-parietal AF (p = 0.008). No significant clusters were found in the right AF. Conclusion: Microstructural development of the CC and the AF in the newborn is associated with receptive language at 12 months of age, demonstrating that interindividual variation in white matter microstructure is relevant for later language development, and indicating that the neural foundation for language processing is laid well ahead of the majority of language acquisition. This suggests that some origins of impaired language development may lie in the intrauterine and potentially neonatal period of life. Understanding how interindividual differences in neonatal brain maturity relate to the acquisition of function, particularly during early development when the brain is in an unparalleled window of plasticity, is key to identifying opportunities for harnessing neuroplasticity in health and disease

Prenatal Stress and Stress Physiology Influences Human Fetal and Infant Development

Prenatal stress has been proposed as a risk factor that may have developmental consequences persisting throughout the lifespan. Exposing rodents to stress during pregnancy has consequences for brain development, stress regulation, learning, emotionality (increased anxiety), and social behavior (increased withdrawal) of the offspring (Weinstock, 2001; Chapillon et al., 2002). Additionally, non-human primates who experience stress during pregnancy have offspring with enhanced behavioral reactivity to stressors later in life (Clarke et al., 1994), lowered levels of motor behavior (Schneider, 1992), compromised neuromotor responses (Schneider and Coe, 1993), irritable temperament (Schneider et al., 1992), and attentional problems (Schneider et al., 1999).https://digitalcommons.chapman.edu/psychology_books/1014/thumbnail.jp

Longitudinal Metabolomic Profiling of Amino Acids and Lipids across Healthy Pregnancy

Pregnancy is characterized by a complexity of metabolic processes that may impact fetal development and ultimately, infant health outcomes. However, our understanding of whole body maternal and fetal metabolism during this critical life stage remains incomplete. The objective of this study is to utilize metabolomics to profile longitudinal patterns of fasting maternal metabolites among a cohort of non-diabetic, healthy pregnant women in order to advance our understanding of changes in protein and lipid concentrations across gestation, the biochemical pathways by which they are metabolized and to describe variation in maternal metabolites between ethnic groups. Among 160 pregnant women, amino acids, tricarboxylic acid (TCA) cycle intermediates, keto-bodies and non-esterified fatty acids were detected by liquid chromatography coupled with mass spectrometry, while polar lipids were detected through flow-injected mass spectrometry. The maternal plasma concentration of several essential and non-essential amino acids, long-chain polyunsaturated fatty acids, free carnitine, acetylcarnitine, phosphatidylcholines and sphingomyelins significantly decreased across pregnancy. Concentrations of several TCA intermediates increase as pregnancy progresses, as well as the keto-body β-hydroxybutyrate. Ratios of specific acylcarnitines used as indicators of metabolic pathways suggest a decreased beta-oxidation rate and increased carnitine palmitoyltransferase-1 enzyme activity with advancing gestation. Decreasing amino acid concentrations likely reflects placental uptake and tissue biosynthesis. The absence of any increase in plasma non-esterified fatty acids is unexpected in the catabolic phase of later pregnancy and may reflect enhanced placental fatty acid uptake and utilization for fetal tissue growth. While it appears that energy production through the TCA cycle increases as pregnancy progresses, decreasing patterns of free carnitine and acetylcarnitine as well as increased carnitine palmitoyltransferase-1 rate and β-hydroxybutyrate levels suggest a concomitant upregulation of ketogenesis to ensure sufficient energy supply in the fasting state. Several differences in metabolomic profiles between Hispanic and non-Hispanic women demonstrate phenotypic variations in prenatal metabolism which should be considered in future studies

Fetal Programming of Body Composition, Obesity, and Metabolic Function: The Role of Intrauterine Stress and Stress Biology

Epidemiological, clinical, physiological, cellular, and molecular evidence suggests that the origins of obesity and metabolic dysfunction can be traced back to intrauterine life and supports an important role for maternal nutrition prior to and during gestation in fetal programming. The elucidation of underlying mechanisms is an area of interest and intense investigation. In this perspectives paper we propose that in addition to maternal nutrition-related processes it may be important to concurrently consider the potential role of intrauterine stress and stress biology. We frame our arguments in the larger context of an evolutionary-developmental perspective that supports roles for both nutrition and stress as key environmental conditions driving natural selection and developmental plasticity. We suggest that intrauterine stress exposure may interact with the nutritional milieu, and that stress biology may represent an underlying mechanism mediating the effects of diverse intrauterine perturbations, including but not limited to maternal nutritional insults (undernutrition and overnutrition), on brain and peripheral targets of programming of body composition, energy balance homeostasis, and metabolic function. We discuss putative maternal-placental-fetal endocrine and immune/inflammatory candidate mechanisms that may underlie the long-term effects of intrauterine stress. We conclude with a commentary of the implications for future research and clinical practice

Correspondence between hair cortisol concentrations and 30-day integrated daily salivary and weekly urinary cortisol measures

Characterization of cortisol production, regulation and function is of considerable interest and relevance given its ubiquitous role in virtually all aspects of physiology, health and disease risk. The quantification of cortisol concentration in hair has been proposed as a promising approach for the retrospective assessment of integrated, long-term cortisol production. However, human research is still needed to directly test and validate current assumptions about which aspects of cortisol production and regulation are reflected in hair cortisol concentrations (HCC). Here, we report findings from a validation study in a sample of 17 healthy adults (mean ± SD age: 34 ± 8.6 yrs). To determine the extent to which HCC captures cumulative cortisol production, we examined the correspondence of HCC, obtained from the first 1cm scalp-near hair segment, assumed to retrospectively reflect 1-month integrated cortisol secretion, with 30-day average salivary cortisol area-under-the curve (AUC) based on 3 samples collected per day (on awakening, +30 min, at bedtime) and the average of 4 weekly 24-hr urinary free cortisol (UFC) assessments. To further address which aspects of cortisol production and regulation are best reflected in the HCC measure, we also examined components of the salivary measures that represent: 1) production in response to the challenge of awakening (using the cortisol awakening response [CAR]), and 2) chronobiological regulation of cortisol production (using diurnal slope). Finally, we evaluated the test-retest stability of each cortisol measure. Results indicate that HCC was most strongly associated with the prior 30-day integrated cortisol production measure (average salivary cortisol AUC) (r = 0.61, p = 0.01). There were no significant associations between HCC and the 30-day summary measures using CAR or diurnal slope. The relationship between 1-month integrated 24-hr UFC and HCC did not reach statistical significance (r = 0.30, p = 0.28). Lastly, of all cortisol measures, test-retest correlations of serial measures were highest for HCC (month-to-month: r = 0.84, p < 0.001), followed by 24-hr UFC (week-to-week: r’s between 0.59 and 0.68, ps < 0.05) and then integrated salivary cortisol concentrations (week-to-week: r’s between 0.38 and 0.61, p’s between 0.13 and 0.01). These findings support the contention that HCC provides a reliable estimate of long-term integrated free cortisol production that is aligned with integrated salivary cortisol production measured over a corresponding one-month period

A novel maturation index based on neonatal diffusion tensor imaging reflects typical perinatal white matter development in humans

Human birth presents an abrupt transition from intrauterine to extrauterine life. Here we introduce a novel Maturation Index (MI) that considers the relative importance of gestational age at birth and postnatal age at scan in a General Linear Model. The MI is then applied to Diffusion Tensor Imaging (DTI) in newborns for characterizing typical white matter development in neonates. DTI was performed cross-sectionally in 47 neonates (gestational age at birth=39.1±1.6 weeks [GA], postnatal age at scan=25.5±12.2days [SA]). Radial diffusivity (RD), axial diffusivity (AD) and fractional anisotropy (FA) along 27 white matter fiber tracts were considered. The MI was used to characterize inflection in maturation at the time of birth using GLM estimated rates of change before and after birth. It is proposed that the sign (positive versus negative) of MI reflects the period of greatest maturation rate. Two general patterns emerged from the MI analysis. First, RD and AD (but not FA) had positive MI on average across the whole brain (average MIAD=0.31±0.42, average MIRD=0.22±0.34). Second, significant regions of negative MI in RD and FA (but not AD) were observed in the inferior corticospinal regions, areas known to myelinate early. Observations using the proposed method are consistent with proposed models of the white matter maturation process in which pre-myelination is described by changes in AD and RD due to oligodendrocyte proliferation while true myelination is characterized by changes in RD and FA due to myelin formation

Variation in the Maternal Corticotrophin Releasing Hormone-Binding Protein (CRH-BP) Gene and Birth Weight in Blacks, Hispanics and Whites

Background: Given the unique role of the corticotrophin-releasing hormone (CRH) system in human fetal development, the aim of our study was to estimate the association of birth weight with DNA sequence variation in three maternal genes involved in regulating CRH production, bioavailability and action: CRH, CRH-Binding Protein (CRH-BP), and CRH type 1 receptor (CRH-R1), respectively, in three racial groups (African-Americans, Hispanics, and non-Hispanic Whites). Methods: Our study was carried out on a population-based sample of 575 mother-child dyads. We resequenced the three genes in mouse-human hybrid somatic cell lines and selected SNPs for genotyping. Results: A significant association was observed in each race between birth weight and maternal CRH-BP SNP genotypes. Estimates of linkage disequilibrium and haplotypes established three common haplotypes marked by the rs1053989 SNP in all three races. This SNP predicted significant birth weight variation after adjustment for gestational age, maternal BMI, parity, and smoking. African American and Hispanic mothers carrying the A allele had infants whose birth weight was on average 254 and 302 grams, respectively, less than infants having C/C mothers. Non-Hispanic White mothers homozygous for the A allele had infants who were on average 148 grams less than those infants having A/C and C/C mothers. Conclusions: The magnitudes of the estimates of the birth weight effects are comparable to the combined effects of multiple SNPs reported in a recent meta-analysis of 6 GWAS studies and is quantitatively larger than that associated with maternal cigarette smoking. This effect was persistent across subpopulations that vary with respect to ancestry and environment. © 2012 Wadhwa et al

Effects of Antenatal Maternal Depressive Symptoms and Socio-Economic Status on Neonatal Brain Development are Modulated by Genetic Risk

This study included 168 and 85 mother-infant dyads from Asian and United States of America cohorts to examine whether a genomic profile risk score for major depressive disorder (GPRSMDD) moderates the association between antenatal maternal depressive symptoms (or socio-economic status, SES) and fetal neurodevelopment, and to identify candidate biological processes underlying such association. Both cohorts showed a significant interaction between antenatal maternal depressive symptoms and infant GPRSMDD on the right amygdala volume. The Asian cohort also showed such interaction on the right hippocampal volume and shape, thickness of the orbitofrontal and ventromedial prefrontal cortex. Likewise, a significant interaction between SES and infant GPRSMDD was on the right amygdala and hippocampal volumes and shapes. After controlling for each other, the interaction effect of antenatal maternal depressive symptoms and GPRSMDD was mainly shown on the right amygdala, while the interaction effect of SES and GPRSMDD was mainly shown on the right hippocampus. Bioinformatic analyses suggested neurotransmitter/neurotrophic signaling, SNAp REceptor complex, and glutamate receptor activity as common biological processes underlying the influence of antenatal maternal depressive symptoms on fetal cortico-limbic development. These findings suggest gene-environment interdependence in the fetal development of brain regions implicated in cognitive-emotional function. Candidate biological mechanisms involve a range of brain region-specific signaling pathways that converge on common processes of synaptic development